Calcium and Magnesium in Relation to Colorectal Neoplasia, Lipid Profile and Uric Acid
It is plausible that calcium intake and the calcium: magnesium (Ca:Mg) intake ratio play an essential role in the development of colorectal cancer. The first project of this dissertation was to determine the role of calcium intake and its interaction with Ca:Mg intake ratio in risks of incident adenoma, metachronous adenoma, and colorectal cancer using the data from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO). The study included incident colorectal adenoma (1,147 cases), metachronous adenoma (855 cases) and incident colorectal cancer (697 and 578 cases in intervention and control arms, respectively) among 108,563 PLCO participants aged 55 to 74 years. Compared to low calcium intake (<600 mg/day), higher intakes of calcium were associated with suggestive reduced risk of advanced and/or synchronous adenomas and significantly reduced risk of colorectal cancer, especially for distal colorectal cancer. No such evidence was found for incident colorectal adenoma. The inverse association between calcium intake and advanced and/or synchronous adenoma, were primarily appeared in participants with Ca:Mg ratios ranging from 1.7 to 2.5. In addition, the significant association between calcium intake and risk of incident distal colorectal cancer appeared to be primarily in the control arm without regular endoscopy. The second and third projects of this dissertation were to examin whether reducing the Ca:Mg intake ratio through magnesium supplementation change levels of lipid biomarkers and uric acid among participants with Ca:Mg intake ratio ≥ 2.6 in the Personalized Prevention of Colorectal Cancer Trial (PPCCT). Among 150 participants in the PPCCT study who finished the trial, overall, magnesium treatment did not significantly affect lipid profile including low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-c), triglycerides, total cholesterol, and uric acid. Among participants with long-term high Ca:Mg ratio, magnesium supplementation led to a statistically significant increase of HDL-c level by 5 mg/dl. This study provides additional evidence to understand the modifying effect of Ca:Mg intake ratios on the association between calcium intake and risk of colorectal cancer development at various stages.